The importance of glutathione and glutathione transferase for somatic mutations in Drosophila melanogaster induced in vivo by 1,2-dichloroethane

Carcinogenesis
L RomertC Ramel

Abstract

Two principal pathways of metabolism of the carcinogenic compound 1,2-dichloroethane (DCE) have been proposed. One is a mixed function oxidase dependent pathway requiring oxygen and NADPH. The other pathway depends on the presence of glutathione (GSH) and glutathione transferase (GST). The aim of this study was to investigate the role of the latter pathway for the in vivo mutagenicity of DCE in the somatic wing spot test in Drosophila melanogaster. DCE caused a dose-dependent increase of wing spots. In order to investigate the role of cellular GSH for the mutagenicity, the level of GSH was decreased by 24 h pretreatment with buthionine sulfoximine (BSO), an efficient inhibitor of GSH synthesis. This pretreatment decreased the GSH level to approximately 6% as compared to the control. The pretreatment also resulted in a significant decrease of the mutagenicity of DCE. Treatment of the larvae with phenobarbiturate (PB) resulted in approximately 200% induction of cytosolic GST, and a corresponding increase in the DCE mutagenicity. These results indicate that the important pathway in vivo for the mutagenicity of DCE is dependent on GSH and GST. A similar experimental protocol was used to study interactions between aflatoxin B1 (AFB)...Continue Reading

Citations

Sep 5, 1998·Mutation Research·U GrafF E Würgler
Sep 25, 1999·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·S K Abraham, S P Singh
Jan 1, 1993·Insect Molecular Biology·R A Reiss, A A James
Jan 1, 1992·Critical Reviews in Biochemistry and Molecular Biology·S Tsuchida, K Sato
Jan 25, 2011·Mutation Research·Maureen R GwinnKathryn Z Guyton
Sep 3, 2005·International Braz J Urol : Official Journal of the Brazilian Society of Urology·Silvio TucciJose E S Roselino

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